Improved Methodology for the Preparation of Chiral Amines
Improved Methodology for the Preparation of Chiral Amines
Improved Methodology for the Preparation of Chiral Amines
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
1.5.4. Stereoselective Conversion <strong>of</strong> Prochiral Substrates to Enantiopure<br />
Compounds (Asymmetric Syn<strong>the</strong>sis)<br />
In asymmetric syn<strong>the</strong>sis a stereogenic centre is created under <strong>the</strong> influence <strong>of</strong> some external<br />
or internal chiral inducing agents. This strategy can be subdivided into three approaches:<br />
substrate-controlled approach; chiral auxiliary approach; and catalyst controlled approach. In<br />
substrate controlled approach, chirality is present internally within <strong>the</strong> molecule directing<br />
remaining groups or faces in stereoselective manner. Limitations <strong>of</strong> this approach come from<br />
<strong>the</strong> fact that enantiopure starting materials are not easily available and <strong>the</strong> reacting sites<br />
should be within close proximity to <strong>the</strong> chiral centre.<br />
Regarding <strong>the</strong> o<strong>the</strong>r two approaches, achiral molecule is converted into chiral entity utilizing<br />
ei<strong>the</strong>r a stoichiometric quantity <strong>of</strong> <strong>the</strong> chiral auxiliary or a catalytic quantity <strong>of</strong> chiral<br />
catalysts. In <strong>the</strong> chiral auxiliary approach, chirality is induced in achiral molecule utilizing<br />
external chiral entity through <strong>for</strong>ming covalent bond with <strong>the</strong> achiral starting material. This<br />
auxiliary is <strong>the</strong>n cleaved from <strong>the</strong> final product in an additional step. Special precautions<br />
should be taken to avoid any racemisation <strong>of</strong> <strong>the</strong> final product in <strong>the</strong> deportation step. One<br />
example <strong>of</strong> this auxiliary approach is shown in scheme 1.6 in which (1S,2S)-(+)-<br />
pseudoephedrine is used as <strong>the</strong> chiral auxiliary to produce diastereomeric alkylated<br />
pseudoephedrine amides which can <strong>for</strong>m enantioenriched carboxylic acids(by hydrolysis),<br />
alcohols and aldehydes (by reduction). [35]<br />
15